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IUPUI Researcher publishes promising findings of novel approaches to treating cancer. 

Fighting Fire with Fire: Approaches to Tumor Suppression

Dr. Hiroki Yokota, PhD

The biggest breakthroughs in any field are often the result of outside of the box thinking and divergent approaches to solving complex problems. While these novel methods may initially generate resistance or even controversy, it is vital that a diversity of ideas be applied when investigating important topics in biomedical research. A prime example of this is the treatment of cancer. With a background in astronautics and expertise in the mechanical stimulation of bone, Dr. Hiroki Yokota, PhD, seeks to discover such unconventional means of suppressing tumor growth in cancer models.

Dr. Yokota, a Professor of Biomedical Engineering and Indiana Center for Musculoskeletal Health Member, recently published his findings from two projects, both of which showed outstanding potential for new lines of inquiry into how cancer is treated. The first study, published in Bone Research, examines mechanical tibial loading as a mechanism to suppress brain tumors through dopamine mediation.

Dopamine is well established as having tumor-suppressing qualities. However, dopamine cannot pass the blood-brain barrier, meaning injecting the neurotransmitter is not an option. This raises the question of how to produce dopamine directly in the brain. One option is through drug induction. With his expertise in the mechanical stimulation of bone, Dr. Yokota believed there was another option as well.

Through earlier studies, Dr. Yokota found that mechanical manipulation not only strengthens bones but is also connected to the brain by neurons and creates dopamine enzymes. He saw this as an alternative approach to producing dopamine in the brain and thus increasing tumor-suppressing factors. To test this, the Yokota Lab used three groups of mouse models all with active tumors: a placebo group, a group being given a dopamine-inducing drug and a group on which mechanical loading was performed via the tibia. They then compared the tumor sizes in each group and found that both the drug-induced and mechanical loading groups saw considerable shrinkage.

Moving forward, this raises many exciting possibilities for the treatment of tumors and other disorders. For instance, the results suggest the mechanical manipulation of bone may also help with the treatment of Parkinson’s Disease. At the very least, the study provides a strong foundational baseline to develop new treatment options that can be used in conjunction with the current drug-based therapies

The second study recently published by the lab looks at an extremely novel and surprising method of suppressing tumor activity. Published in Theranostics, the findings of this project show that by using known tumor-promoting chemicals one can produce protein-rich secretome that acts as a tumor suppressor. These results are quite controversial and raise many questions.

The typical approach to treat a cancerous tumor is to apply chemical compounds known to kill tumors cells. However, one of the major downsides to this method is that when a tumor is attacked by these drugs, it produces secretome that promotes tumor growth in the surrounding area. This means that even if the initial drug-based treatment is successful in killing off the original tumor, there is an increased chance of a new tumor developing in the area.

However, the opposite mechanism is also true. If a tumor is allowed to grow without interference, it produces secretome chock-full of proteins that suppress tumor growth in the surrounding area. This discovery informed Dr. Yokota’s lab’s line of inquiry: how can we harness the tumor-suppressive qualities of the secretome created by a thriving tumor?

Their answer was to create a conditioned medium using known tumor growing factors and then inject this medium into mouse models with tumors in the mammary pad and bone. What they found was that although these mediums were made up of tumor-promoting factors, when they’re introduced extracellularly, they produce measurable tumor shrinkage.

This technique raises obvious questions due to its paradoxical approach. However, the data clearly shows that artificially conditioned mediums can harness the tumor-killing proteins produced by growing tumors themselves.

Ultimately there is much more investigation to be done here. The lab’s next step is to begin looking at the specific groups of proteins in these mediums and identifying which groups produce the best results. In the long run, they hope to determine if these mediums can help supplement existing treatments, either by increasing effectiveness or by lowering the required dose of the current therapy (thereby reducing side effects).

The Yokota Lab is currently pursuing external funding to expand on these findings and move toward clinical applications.


Both publications can be read in full here:

Mechanical tibial loading remotely suppresses brain tumors by dopamine-mediated downregulation of CCN4

Generation of the tumor-suppressive secretome from tumor cells


Written by Kyle Bone, ICMH Operations Manager

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IU School of Medicine

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